Other Articles in This Child Health Theme Issue of JAMA

EMBARGOED FOR EARLY RELEASE: 10 A.M. (ET) TUESDAY, APRIL 30, 2013

Antiretroviral Regimen Associated With Less Virological Failure Among HIV-Infected Children

Elizabeth D. Lowenthal, M.D., M.S.C.E., of the University of Pennsylvania Perelman School of Medicine and Children’s Hospital of Philadelphia, and colleagues conducted a study to determine whether there was a difference in time to virological failure between HIV-infected children initiating nevirapine vs. efavirenz-based antiretroviral treatment in Botswana.

“More than 2 million children worldwide are infected with human immunodeficiency virus (HIV), approximately 90 percent of whom live in sub-Saharan Africa,” according to background information in the article. “Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with HIV infection. Data on the comparative effectiveness of these medications in children are limited. … Most countries favor nevirapine-based regimens for the majority of children due to perceived comparable effectiveness at lower cost.”

The study included children (3-16 years of age) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. The primary outcome was time from initiation of therapy to virological failure, defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression.

With a median (midpoint) follow-up time of 69 months, the researchers found that 57 children (13.5 percent) initiating treatment with efavirenz and 101 children (26.4 percent) initiating treatment with nevirapine had virological failure. There were 11 children (2.6 percent) receiving efavirenz and 20 children (5.2 percent) receiving nevirapine who never achieved virological suppression.

“In this large cohort of children infected with HIV, time to virological failure was longer among children receiving efavirenz vs. nevirapine. With the majority of the world’s children receiving nevirapine-based antiretroviral therapy, these findings may have significant public health importance,” the authors write. “… more work should be done to make efavirenz a cost-effective option for pediatric antiretroviral treatment programs in resource-limited settings.”

Study Examines Neurodevelopmental Outcomes For Children Born Extremely Preterm

Fredrik Serenius, M.D., Ph.D., of Uppsala University, Uppsala, Sweden, and colleagues conducted a study to assess neurological and developmental outcome in extremely preterm (less than 27 gestational weeks) children at 2.5 years.

“A proactive approach to resuscitation and intensive care of extremely preterm infants has increased survival and lowered the gestational age of viability. There are concerns that increased survival may come at the cost of later neurodevelopmental disability among survivors. Approximately 25 percent of extremely preterm infants born in the 1990s had a major disability at preschool age, such as impaired mental development, cerebral palsy, blindness, or deafness. More recent studies report decreasing, unchanged, or increasing rates of neurodevelopmental disability at preschool age compared with previous decades,” according to background information in the article.

The study included extremely preterm infants born in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69 percent) survived to 2.5 years. Survivors were assessed and compared with control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. Cognitive, language, and motor development were assessed. Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age.

At a median (midpoint) age of 30.5 months, 456 of 491 (94 percent) extremely preterm children were evaluated (41 by chart review only). The researchers found that overall, 42 percent of extremely preterm children had no disability (compared with 78 percent of control participants), 31 percent had mild disability, 16 percent had moderate disability, and 11 percent had severe disability. There was an increase in moderate or severe disabilities with decreasing gestational age. Also, the difference in overall outcome between preterm boys and girls was not statistically significant.

“Improved survival did not translate into increasing disability rates, and we like others believe that the neurodevelopmental outcome for extremely preterm children born in the 2000s will be better than for those born in the 1990s. Nevertheless, the impact of prematurity on neurodevelopmental outcome was large, which calls for further improvements in neonatal care, such as better control of infection and postnatal nutrition,” the authors write.

No Association Found Between Children with Autism and Markers of Lyme Disease

“A proposed link between Lyme disease and autism has garnered considerable attention. Among individuals with autism spectrum disorders, rates of seropositivity for Lyme disease of greater than 20 percent have been reported. However, controlled studies to assess serological evidence of infection with Borrelia burgdorferi (the causative agent of Lyme disease) in patients with autism are lacking,” writes Mary Ajamian, M.S., of Columbia University Medical Center, New York, and colleagues.

As reported in a Research Letter, the authors performed Lyme disease serological testing on serum samples from children with and without autism. For the analysis, 70 children with autism (58 male; average age, 7.2 years) and 50 unaffected controls (32 male; average age, 9.0 years) were included.

“None of the children with autism or unaffected controls had serological evidence of Lyme disease by 2-tier testing,” the authors write. “The data do not address whether Lyme disease may cause autism-like behavioral deficits in some cases. However, the study’s sample size is large enough to effectively rule out the suggested high rates of Lyme disease or associated seroprevalence among affected children.”

The National Children’s Study, a National Institutes of Health study (proposed in 2004) was originally designed to enroll 100,000 pregnant women in a nationally representative sample of 105 communities. “Yet, in 2013, the study is still in its pilot phase,” writes Nigel Paneth, M.D., M.P.H., of Michigan State University, East Lansing. In this Viewpoint, Dr. Paneth discusses some of the flaws in the study and provides suggestions for moving forward.

“At the heart of the failure of the National Children’s Study (NCS) is its abandonment of the hypothetico-deductive mode of scientific thinking. Vacillation in study design was inevitable once the National Institutes of Health (NIH ) asserted, in 2010, that the NCS ‘is not designed to answer a set of specific hypotheses. It is a data-gathering platform.’ Without explicit scientific goals, there is no logical way to select an optimal design.”

“Hypothesis-driven research on a large, representative sample of children is needed because progress on prevention of childhood diseases has stalled and many childhood diseases are uncommon,” he writes. “An optimum study design for the NCS would be powered to enumerate, for the first time, the frequency of important maternal and child health conditions in a nationally representative sample. It would also provide unbiased absolute estimates of the risk of those conditions in relation to characteristics such as race, ethnicity, social class, and geography, advancing understanding of the nature of health disparities. Most importantly, it would take the first steps to prevention by rigorously testing clearly delineated hypotheses about the environmental origins of important and burdensome childhood disorders.”

The Transformation of Child Health Research – Innovation, Market Failure, and the Public Good

Barbara J. Stoll, M.D., of the Emory University School of Medicine and Children’s Healthcare of Atlanta, and colleagues write that “… the pediatric research community faces mounting evidence that the nature and scope of current research are inadequate. … For measurable and sustainable gains in child health, pediatric research should be informed by the changing epidemiology of childhood illness, the need to monitor both survival and long-term outcomes, and the increasing recognition of pediatric origins of adult chronic disease and social determinants of health.”

In this Viewpoint, the authors suggest measures to improve child health research.

“Child health research at its best provides a model for the advancement of knowledge to improve health and health care. The challenges confronting pediatric research reflect the need to respond to the changing milieu of child health and disease and to look beyond survival to consider the long-term consequences of pediatric health and disease. This transition will require innovative partnerships, a cadre of well-trained investigators interested in child health, and creative use of emerging technologies. It will also require linkage of research priorities to larger societal forces and a renewed commitment to advancing the interests of children in an increasingly fractious policy world.”

Creation and Retention of the Next Generation of Physician-Scientists for Child Health Research

“Over the last 30 years, proportionately fewer physician-scientists capable of sustaining a research program have committed to a hypothesis-driven research career focused on child-health issues,” writes David N. Cornfield, M.D., of the Stanford University School of Medicine, Stanford, Calif., and colleagues.

In this Viewpoint, the authors examine the challenges to increasing the number of physician-scientists for child health research and strategies to address the issue.

“Development of the pediatric physician-scientist pathway can be facilitated by relatively straightforward and resource-efficient investments. Motivating even this relatively modest investment demands explicit acknowledgment of the value of the clinician-scientist. Children will be well served when more children’s hospitals and pediatric departmental resources are focused on creation, retention, and promotion of the engine that has powered their growth and increasing prominence—i.e., physician-scientists creating and translating knowledge into care. Without such recognition and resolve, pediatrics as a discipline may be unable to meet its collective obligation to the next generations.”

The June 9 issue of JAMA was a theme issue on the Americans with Disabilities Act. News Releases: Overall Rate of Traumatic Spinal Cord Injury Remains Stable in U.S. Control System Shows Potential for Improving Function of Powered Prosthetic Leg MCAT Predicts Differently for Students Who Test with Extra Time; Suggests…

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